The present invention generally shows methods and device embodiments that use extracorporeal acoustic pressure shock waves for preventing and treating living tissue infections for mammals (humans and animals) in order to produce tissue disinfection.
From the treatment point of view, the preferred approach is the use of parental and local antibiotics. Numerous modern commercial antibacterial agents are available for treating infections as penicillin, oxytetracycline, chlortetracycline, cloxacillin, cephapirin, ampicilin, dihydrostreptomycin, ceftiofur, gentamicin, erythromycin, spiramycin, novobiocin, oxazolidinone, etc. The global concerns for developing antimicrobial drug resistance and the need to develop more prudent and judicious use of drugs have caused the necessity of finding new approaches to treat infections that do not display these disadvantages. Also, sometimes the infections are very difficult to treat due to the fact that they are located deep inside the body and in places where the reach of significant amounts of antibiotics is difficult, without significant side effects. One notorious example is the treatment of infections of human joints implants. In general micro-organisms that produce infection are easy to kill by antibiotics, if they are in a planktonic stage. However, in the case of implants (hip, knee, etc.) they multiply and group to form biofilms around the implant, which makes the drugs inefficient. The drugs cannot penetrate biofilms and after extensive antibiotic therapies that last up to one year, the ultimate solution is to take the implant out, which represents a significant distress to the patient and a major financial burden to modern society.
This invention also shows embodiments for preventing the onset of mastitis and treatment of mastitis in female mammals with shock waves. For humans, mastitis is most common during the first 6 months of breast-feeding and although mastitis can be discouraging and painful, it is usually easily cleared up with medicine/drugs. This is why this invention relates especially to the prevention and treatment of mastitis in milking mammals/animals, including, for example, bovine, ovine and caprine, and more specifically to either therapeutically or prophylactically treatment of cows, sheep ewes and goats against mastitis, as well as the product, which is used in the treatment.
For milking mammals/animals, mastitis is the inflammation of the mammary gland or udder tissue. It usually occurs as an immune response to bacterial invasion of the teat canal by variety of bacterial sources present on the farm (infectious mastitis), and can also occur as a result of non-infectious factors as chemical, mechanical, or thermal injury to the udder. Milk-secreting tissues and various ducts throughout the udder can be damaged by bacterial/micro-organisms toxins, and sometimes permanent damage to the udder occurs. Severe acute cases can be fatal, but even in animals that recover there may be consequences for the rest of the lactation and subsequent lactations.
Despite decades of research and steady progress, mastitis remains the most costly infectious disease affecting dairy herds. Due to mastitis contagious environmental micro-organisms can be spread through the herds and the produced milk is infected, which makes the milk unusable for consumption. The environmental micro-organisms can infect the animals not only during milking periods but also during the dry periods.
Maximizing/supplementing the animal's immunological defense and minimizing bacterial challenge from the environment represent two main principles used to prevent new mastitis infections. Mastitis treatment and control is one of the largest costs to the dairy industry and a significant factor in dairy cow welfare. Losses arise from: 1) milk thrown away due to contamination by medication/antibiotics or being unfit to drink; 2) reduction in yields due to illness and any permanent damage to udder tissue; 3) extra labor required to tend to mastitic cows; 4) costs of veterinary care, medicines; and reduced longevity due to premature culling.
When mastitis infection is present it can be broken down into following categories, dependent upon the signs and symptoms.
Subclinical mastitis represents the presence of an infection without apparent signs of local inflammation or systemic involvement. Although transient episodes of abnormal milk may appear, these infections are for the most part asymptomatic and, if the infection persists for at least 2 months, it is termed as chronic. Once established, many of these infections persist for entire lactations or the life of the cow.
Subacute mastitis shows small inflammation of the mammary gland/udder without showing any signs of fever or depression or any other systemic involvement.
Clinical mastitis (peracute and acute) is an inflammatory response to infection causing visibly abnormal milk (eg. color, fibrin clots). As the extent of the inflammation increases, changes in the udder (swelling, heat, pain, redness) may also be apparent. For clinical mastitis where the udder is swollen, hot, and red can be defined as peracute mastitis. The cow may flinch or kick when the bag/udder is touched because it is sensitive. Milk production is reduced. A general fever may be present, depression, shivering, rapid weight loss, and appetite loss occurs in many cases. For clinical mastitis where severe inflammation is present and includes systemic involvement (severe fever, anorexia, shock, mild depression, weakness, diarrhea and inactive animal), the case is termed severe or acute mastitis. In very severe/acute mastitis cases death may also occur.
Mastitis infections are produced by almost any microbe that can opportunistically invade udder tissue and cause infection. However, most infections are caused by various species of gram-positive cocci as streptococci, staphylococci, and gram-negative rods such as Klebsiella sp, Serratia marcescens, Pseudomonas aeruginosa, Escherichia coli or lactose-fermenting organisms of enteric origin, commonly termed coliforms. Mastitis can also be produced by other atypical pathogens such as mycotic and algal microbes.
Except for Mycoplasma spp, which may spread from cow to cow through aerosol transmission and invade the udder subsequent to bacteremia, contagious pathogens are spread during milking process. Species that use this mode of transmission include Staphylococcus aureus, Streptococcus agalactiae, and Corynebacterium bovis. Additionally, contagious transmission infrequently occurs for pathogens typically associated with environmental reservoirs, through the development of host-adapted virulence factors (Escherichia coli) or by shedding of overwhelming numbers of bacteria from infected udders (Trueperella pyogenes).
From the treatment point of view the preferred approach is the use of parental and intra-mammary antibiotics. However, systemic therapy involves extra-label drug use, and milk/meat withholding periods must be determined judiciously. U.S. Pat. No. 2,968,592 teaches the use of penicillin. Numerous modern commercial antibacterial agents are available for treating mastitis besides penicillin and include oxytetracycline, chlortetracycline, cloxacillin, cephapirin, ampicilin, dihydrostreptomycin, ceftiofur, gentamicin, erythromycin, spiramycin, novobiocin, oxazolidinone (U.S. Pat. No. 6,562,820 teaches the use of oxazolidinone in the treatment of cow mastitis), etc. However, the majority of these drugs are not approved for use in dairy cows (off-label use). Also, the global concerns for developing antimicrobial drug resistance and the need to develop more prudent and judicious use of animal drugs have caused the farmers to reconsider the intervention methods of treating and controlling mastitis.
The delivery of the drugs used for mastitis is well covered. U.S. Pat. No. 4,011,312 teaches a prolonged release drug dosage form for the treatment of bovine mastitis, specifically suited for dry cow treatment, consists of an antimicrobial agent dispersed in a matrix of a low molecular weight polyester of glycolic and lactic acids, and shaped as a cylindrical bougie for facile insertion into the teat canal.
New methods for delivering the antibacterial agents in the area affected by mastitis are mentioned in other patents. For example the EP 2,578,209 patent teaches the delivery of the drugs via nano-particles, thus avoiding the inconvenience of the use of high doses of drugs used in conventional formulations, thus contributing to an improvement in milk quality.
Besides antibacterial agents, the U.S. Pat. No. 3,917,818 teaches the use of immune-globulin obtained from the pooled blood of cows suffering from mastitis.
As a novel method to treat mastitis, the U.S. Pat. No. 5,797,872 teaches the use of chemotherapy agents. Other methods used to treat mastitis without the use of antibiotics are clay therapy, homeopathy, phytotherapy, oxygen therapy, injection of egg whites into the teat, injections of copper sulphate, calcium oxide and neem oil into the udder, acupuncture, antibodies, etc. For example the U.S. Pat. No. 5,846,543 teaches the use of natural components (Echinechea Goldenseal Supreme; Wild Ginseng Supreme; gelsemium, pokeroot, and aconite; and aloe vera juice) for the phytotherapy treatment of cow mastitis.
Organic dairy farmers, having limited use of antibiotic treatments, often use alternative therapies such as homeopathy for the treatment of mastitis.
Other approach to treat mastitis is based on the increased/stimulated reaction of the animal immune system to the pathogen, via vaccination. Thus the U.S. Pat. No. 5,198,214 teaches the use of a polyvalent vaccine effective in the prevention and treatment of mastitis in bovine animals. For vaccine creation is done by periodically culturing the milk of animals exhibiting preclinical mastitis to cultivate any pathogens present therein, killing those pathogens and incorporating each strain of cultivated, killed pathogen in a pharmacological carrier together with all other strains previously identified.
For prevention of mastitis for dry/non-lactating animals the U.S. Pat. No. 6,254,881 teaches the creation of a mechanical seal for the teat (to prevent bacterial penetration for dry cows) using approximately 65% by weight of bismuth sub-nitrate in a gel based on aluminium stearate.